Twenty-five years have passed since the discovery of the orexin system, during which time we have learned more and more about it. A number of studies have been conducted showing the role of the orexin system in insomnia, as well as its potential use in the treatment of obesity and depression. In this review, we present the role of the orexin system in the development of depressive illness and show the characteristics of seltorexant, a potential drug for the treatment of depression. This review describes the structure and synthesis of the compound as well as its pharmacodynamics and pharmacokinetics. Pre-clinical and clinical studies are also described, including side effects. There is evidence that the use of seltorexant is considered safe, with no clear or major clinically significant side effects, which makes it a promising candidate for the treatment of depression and anxiety disorders.
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http://dx.doi.org/10.3390/molecules28083575 | DOI Listing |
Handb Clin Neurol
January 2025
Department of Surgical Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy; Department of Neuroscience, Psychology Unit, University of Pisa Azienda Ospedaliera Universitaria Pisana (AUOP), Pisa, Italy.
Insomnia disorder is a frequent sleep disorder leading to significant health and economic consequences. It has been proposed that individuals with insomnia may experience compromised deactivation systems of arousal, leading to a chronic state of hyperactivation of arousal known as hyperarousal, along with instability in the flip-flop system. Such disruptions may have a primarily impact on the sleep homeostatic drive process.
View Article and Find Full Text PDFHandb Clin Neurol
January 2025
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; Sleep Medicine Centre, Neurology Unit, University Hospital of Rome Tor Vergata, Rome, Italy.
Obstructive sleep apnea syndrome (OSAS) significantly affects the sleep-wake circadian rhythm through intermittent hypoxia and chronic sleep fragmentation. OSAS patients often experience excessive daytime sleepiness, frequent awakenings, and sleep fragmentation, leading to a disrupted circadian rhythm and altered sleep-wake cycle. These disruptions may exacerbate OSAS symptoms and contribute to neurodegenerative processes, particularly through the modulation of clock gene expression such as CLOCK, BMAL1, and PER.
View Article and Find Full Text PDFVitam Horm
January 2025
Clinical Research Center, Murayama Medical Center, Musashimurayama, Japan.
The hypothalamus is the gray matter of the ventral portion of the diencephalon. The hypothalamus is the higher center of the autonomic nervous system and is involved in the regulation of various homeostatic mechanisms. It also modulates respiration by facilitating the respiratory network.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Feeding behavior changes induced by opioid addiction significantly contribute to the worsening opioid crisis. Activation of the reward system has shown to provoke binge eating disorder in individuals with opioid use disorder, whereas prolonged opioid exposure leads to weight loss. Understanding the mechanisms underlying these phenomena is essential for addressing this pressing societal issue.
View Article and Find Full Text PDFJ Physiol Sci
January 2025
Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss. Sleep-wake disorders are an extremely predominant and often disabling aspect of AD. Ox is vital in maintaining the sleep-wake cycle and promoting wakefulness.
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